摘要
无义介导的信使RNA(mRNA)降解途径(nonsense-mediated mRNA decay,简称为NMD)是真核生物细胞内一种重要的基因转录后表达调控机制,它积极参与一系列细胞生理和生化过程,控制细胞命运和生命体的组织稳态。NMD的缺陷会导致人类疾病,如神经发育障碍、肿瘤发生和自身免疫疾病等。UPF3(Up-frameshift protein 3)是一个核心的NMD因子,它最早在酵母中被发现。UPF3A和UPF3B是UPF3在生物进化到脊椎动物阶段出现的两个旁系同源物,在NMD中具有激活或抑制的作用。以往研究发现,UPF3B蛋白几乎在所有哺乳动物器官中均有表达,而UPF3A蛋白在除睾丸外的大多数哺乳动物组织中难以被检测到。解释这一现象的假说为:在NMD途径中,UPF3B具有比UPF3A更高的竞争性结合UPF2的能力,UPF3B和UPF2的结合促使UPF3A成为游离状态,而游离的UPF3A蛋白不稳定且易被降解。此假说提示UPF3A和UPF3B在NMD中存在拮抗作用。在本研究中,我们重新定量评估了UPF3A和UPF3B在野生型成年雄性和雌性小鼠的9个主要组织和生殖器官中的mRNA和蛋白表达,结果证实UPF3A在雄性生殖细胞中表达量最高。令人惊讶的是,我们发现在包括大脑和胸腺在内的大多数组织中,UPF3A与UPF3B的蛋白水平相当,而在小鼠脾、肺组织中,UPF3A表达高于UPF3B。公共基因表达数据进一步支持了上述发现。因此,我们的研究表明了UPF3A是小鼠组织中普遍表达的NMD因子。同时,该研究结果推测:在生理条件下,UPF3A和UPF3B蛋白之间不存在竞争抑制,且UPF3A在多种哺乳动物组织的稳态中发挥重要作用。
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Data availability statement
All datasets analyzed in this study are available from the corresponding author upon request.
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Acknowledgments
We thank all members of LI laboratory for the discussion during the study. The research projects conducted in LI laboratory are supported by the Zhejiang Provincial Natural Science Foundation of China (No. LY22C050003), the NHC Key Laboratory of Birth Defect for Research and Prevention (Hunan Provincial Maternal and Child Health Care Hospital, Changsha, China) (Nos. KF2020005 and KF2021008), the National Natural Science Foundation of China (No. 31770871), and the Qilu Youth Scholar Startup Funding of Shandong University. Xin MA is supported by a postdoctoral grant from Qingdao City, Shandong Province (No. QDBSH20230102051), China.
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Tangliang LI designed the experiments and supervised the project. Xin MA performed the experiments and analyzed the data. Xin MA and Tangliang LI wrote the manuscript, which was edited by Yan LI, Chengyan CHEN, Yanmin SHEN, and Hua WANG. All authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
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Xin MA, Yan LI, Chengyan CHEN, Yanmin SHEN, Hua WANG, and Tangliang LI declare that they have no conflicts of interest.
All mice had free access to water and food. All animal care and experiments were performed according to the guidelines of the animal ethics committee in Shandong University, Qingdao, China (license number: SYDWLL-2022-083).
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Supplementary information: Spatial expression of the nonsense-mediated mRNA decay factors UPF3A and UPF3B among mouse tissues
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Ma, X., Li, Y., Chen, C. et al. Spatial expression of the nonsense-mediated mRNA decay factors UPF3A and UPF3B among mouse tissues. J. Zhejiang Univ. Sci. B 24, 1062–1068 (2023). https://doi.org/10.1631/jzus.B2300126
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DOI: https://doi.org/10.1631/jzus.B2300126